Only a few important developments occurred in the field of epidemiology
during the 200-year period following the publication of John Graunt’s Bills
of Mortality. One notable development was the realization that experimental studies could be used to test hypotheses about the laws of mortality. As
described in Chapter 7, these studies involve designed experiments that
investigate the role of some factor or agent in the causation, improvement,
postponement, or prevention of disease.23 Their hallmarks are: (1) the comparison
of at least two groups of individuals (an experimental group and a
“control” group) and (2) the active manipulation of the factor or agent
under study by the investigator (that is, the investigator assigns individuals
either to receive or not to receive a preventive or therapeutic measure).
In the mid-1700s, James Lind conducted one of earliest experimental
studies on the treatment of scurvy, a common disease and cause of death at
the time.24(pp145–148) Although scurvy affected people living on land, sailors
often became sick and died from this disease while at sea. As a ship’s surgeon,
Lind had many opportunities to observe the “epidemiology” of this
disease. His astute observations led him to dismiss the popular ideas that
scurvy was a hereditary or infectious disease and to propose that “the principal
and main predisposing cause” was moist air and that its “occasional
cause” was diet.24(pp64–67,85,91) He evaluated his hypothesis about diet with
the following experimental study After 4 weeks, Lind reported the following: “The consequence was,
that the most sudden and visible good effects were perceived from the use
of the oranges and lemons; one of those who had taken them being at the
end of six days fit for duty. . . . He became quite healthy before we came
into Plymouth which was on the 16th of June. . . . The other was the best
recovered of any in his condition; and being now deem pretty well, was
appointed nurse to the rest of the sick.”24(p146) Lind concluded, “I shall here
only observe, that the result of all my experiments was, that oranges and
lemons were the most effectual remedies for this distemper at sea. I am apt
to think oranges preferable to lemons though perhaps both given together
will be found most serviceable.”24(p148)
Although the sample size of Lind’s experiment was quite small by
today’s standards (12 men divided into six groups of two), Lind followed
one of the most important principles of experimental research—ensuring
that important aspects of the experimental conditions remained similar for
all study subjects. Lind selected sailors whose disease was similarly severe,
who lived in common quarters, and who had a similar diet. Thus, the main
difference between the six groups of men was the dietary addition purposefully
introduced by Lind. He also exhibited good scientific practice by
confirming “the efficacy of these fruits by the experience of others.”24(p148)
In other words, Lind did not base his final conclusions about the curative
powers of citrus fruits on a single experiment, but rather he gathered additional
data from other ships and voyages.
Lind used the results of this experiment to suggest a method for preventing
scurvy at sea. Because fresh fruits were likely to spoil and were difficult
to obtain in certain ports and seasons, he proposed that lemon and
orange juice extract be carried on board.24(pp155–156) The British Navy took
40 years to adopt Lind’s recommendation; within several years of doing so,
it had eradicated scurvy from its ranks.24(pp377–380)